US10730949B2ActiveUtilityA1

Method of treating PVNS with anti-CSF1R antibodies

76
Assignee: FIVE PRIME THERAPEUTICS INCPriority: Dec 22, 2014Filed: Jun 22, 2018Granted: Aug 4, 2020
Est. expiryDec 22, 2034(~8.5 yrs left)· nominal 20-yr term from priority
Inventors:Robert SikorskiJulie HambletonNilacantan Sankar
C07K 2317/94A61K 2039/545C07K 2317/34C07K 16/2866A61K 2039/505C07K 2317/24C07K 2317/76A61K 39/395C07K 2317/92A61P 19/02A61P 35/00A61P 19/04
76
PatentIndex Score
1
Cited by
242
References
35
Claims

Abstract

Methods of treating pigmented villonodular synovitis (PVNS) with antibodies that bind colony stimulating factor 1 receptor (CSF1R) are provided.

Claims

exact text as granted — not AI-modified
The invention claimed is: 
     
       1. A method of treating a proliferative disorder involving a synovial joint and/or tendon sheath in a subject, wherein the proliferative disorder is selected from pigmented villonodular synovitis (PVNS), giant cell tumor of the tendon sheath (GCTTS), tenosynovial giant cell tumor (TGCT) such as diffuse type tenosynovial giant cell tumor (dtTGCt), and PVNS/dtTGCT, comprising administering to the subject an effective amount of an antibody that binds CSF1R, wherein the antibody is selected from:
 a) an antibody comprising a heavy chain comprising the sequence of SEQ ID NO: 39 and a light chain comprising the sequence of SEQ ID NO: 46; 
 b) an antibody comprising a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 15, an HC CDR2 having the sequence of SEQ ID NO: 16, and an HC CDR3 having the sequence of SEQ ID NO: 17, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 18, a LC CDR2 having the sequence of SEQ ID NO: 19, and a LC CDR3 having the sequence of SEQ ID NO: 20; and 
 c) an antibody comprising a heavy chain comprising the sequence of SEQ ID NO: 53 and a light chain comprising the sequence of SEQ ID NO: 60. 
 
     
     
       2. A method of treating pigmented villonodular synovitis (PVNS) in a subject comprising administering to the subject an effective amount of an antibody that binds CSF1R, wherein the antibody is selected from:
 a) an antibody comprising a heavy chain comprising the sequence of SEQ ID NO: 39 and a light chain comprising the sequence of SEQ ID NO: 46; 
 b) an antibody comprising a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 15, an HC CDR2 having the sequence of SEQ ID NO: 16, and an HC CDR3 having the sequence of SEQ ID NO: 17, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 18, a LC CDR2 having the sequence of SEQ ID NO: 19, and a LC CDR3 having the sequence of SEQ ID NO: 20; and 
 c) an antibody comprising a heavy chain comprising the sequence of SEQ ID NO: 53 and a light chain comprising the sequence of SEQ ID NO: 60. 
 
     
     
       3. The method of  claim 1 , wherein the antibody is administered once per week, once per two weeks, once per three weeks, or once per month. 
     
     
       4. The method of  claim 1 , wherein the antibody is administered at a dose of at least 1, at least 2, at least 3, at least 4, at least 8, or at least 10 mg/kg. 
     
     
       5. The method of  claim 2 , wherein the PVNS tumor volume is reduced by at least 30% or at least 40% or at least 50% or at least 60% or at least 70% after administration of at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten doses of the antibody that binds CSF1R. 
     
     
       6. The method of  claim 5 , wherein the tumor volume is tumor volume in a single joint. 
     
     
       7. The method of  claim 6 , wherein the single joint is selected from a hip joint and a knee joint. 
     
     
       8. The method of  claim 5 , wherein the tumor volume is total tumor volume in all joints affected by PVNS. 
     
     
       9. The method of  claim 1 , wherein, prior to administering the first dose of the antibody, the subject received a first therapy selected from surgical synovectomy, radiation beam therapy, radio isotope synovectomy, and joint replacement. 
     
     
       10. The method of  claim 9 , wherein the disorder recurred or progressed after the first therapy. 
     
     
       11. The method of  claim 1 , wherein the antibody is administered prior to a therapy selected from surgical synovectomy, radiation beam therapy, radio isotope synovectomy, and joint replacement, or wherein the tumor is unresectable. 
     
     
       12. The method of  claim 1  wherein the subject has not received prior treatment with a CSF1R inhibitor. 
     
     
       13. The method of  claim 1 , wherein the anti-CSF1R antibody blocks binding of CSF1 and/or IL-34 to CSF1R. 
     
     
       14. The method of  claim 1 , wherein the anti-CSF1R antibody inhibits ligand-induced CSF1R phosphorylation in vitro. 
     
     
       15. The method of  claim 1 , wherein the antibody is a humanized antibody or is huAb1. 
     
     
       16. The method of  claim 1 , wherein the antibody is selected from a Fab, an Fv, an scFv, a Fab′, and a (Fab′) 2 . 
     
     
       17. A method of treating a proliferative disorder involving a synovial joint and/or tendon sheath in a subject, comprising administering to the subject an effective amount of an antibody that binds CSF1R, wherein the antibody is selected from:
 a) an antibody comprising a heavy chain comprising the sequence of SEQ ID NO: 39 and a light chain comprising the sequence of SEQ ID NO: 46; 
 b) an antibody comprising a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 15, an HC CDR2 having the sequence of SEQ ID NO: 16, and an HC CDR3 having the sequence of SEQ ID NO: 17, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 18, a LC CDR2 having the sequence of SEQ ID NO: 19, and a LC CDR3 having the sequence of SEQ ID NO: 20; and 
 c) an antibody comprising a heavy chain comprising the sequence of SEQ ID NO: 53 and a light chain comprising the sequence of SEQ ID NO: 60, wherein the subject experiences at least one of (a) a reduction in joint pain, (b) an increase range of motion in a joint, and (c) an increase in functional capacity of a joint, following at least one dose of the antibody. 
 
     
     
       18. The method of  claim 17 , wherein the antibody is administered at a dose of at least 1 mg/kg. 
     
     
       19. The method of  claim 17 , wherein the antibody is administered at a dose of 1-4 mg/kg. 
     
     
       20. The method of  claim 1 , wherein the subject experiences at least one of (a) a reduction in joint pain, (b) an increase range of motion in a joint, and (c) an increase in functional capacity of a joint, following at least one dose of the antibody. 
     
     
       21. The method of  claim 20 , wherein the antibody is administered at a dose of at least 1 mg/kg. 
     
     
       22. The method of  claim 20 , wherein the antibody is administered at a dose of 1-4 mg/kg. 
     
     
       23. The method of  claim 2 , wherein the subject experiences at least one of (a) a reduction in joint pain, (b) an increase range of motion in a joint, and (c) an increase in functional capacity of a joint, following at least one dose of the antibody. 
     
     
       24. The method of  claim 23 , wherein the antibody is administered at a dose of at least 1 mg/kg. 
     
     
       25. The method of  claim 23 , wherein the antibody is administered at a dose of 1-4 mg/kg. 
     
     
       26. The method of  claim 1 , wherein the antibody is administered at a dose of 1-4 mg/kg. 
     
     
       27. The method of  claim 2 , wherein the antibody is administered at a dose of 1-4 mg/kg. 
     
     
       28. The method of  claim 2 , wherein the anti-CSF1R antibody blocks binding of CSF1 and/or IL-34 to CSF1R. 
     
     
       29. The method of  claim 2 , wherein the anti-CSF1R antibody inhibits ligand-induced CSF1R phosphorylation in vitro. 
     
     
       30. The method of  claim 2 , wherein the antibody is a humanized antibody or is huAb1. 
     
     
       31. The method of  claim 2 , wherein the antibody is selected from a Fab, an Fv, an scFv, a Fab′, and a (Fab′) 2 . 
     
     
       32. The method of  claim 17 , wherein the anti-CSF1R antibody blocks binding of CSF1 and/or IL-34 to CSF1R. 
     
     
       33. The method of  claim 17 , wherein the anti-CSF1R antibody inhibits ligand-induced CSF1R phosphorylation in vitro. 
     
     
       34. The method of  claim 17 , wherein the antibody is a humanized antibody or is huAb1. 
     
     
       35. The method of  claim 17 , wherein the antibody is selected from a Fab, an Fv, an scFv, a Fab′, and a (Fab′) 2 .

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